Selective effects of long-term lithium and carbamazepine administration on G-protein subunit expression in rat brain.
The efficacy of lithium and carbamazepine in treatment of bipolar affective disorder is well established. Although a number of biochemical effects have been found the exact molecular mechanisms underlying their therapeutic actions have not been elucidated. Nor have the target regions in the brain been located. The objectives of the present investigation were to identify the selective effects and target regions of long-term treatment, with either lithium or carbamazepine, on G-protein subunit expression in rat brain. Effects were measured in hippocampus, hypothalamus, amygdala, frontal cortex, neostriatum, thalamus, raphe nuclei and cerebellum. At the protein level amounts of Galphao decreased significantly (P < 0.01) in neostriatum and Gbeta increased in frontal cortex in response to both drug treatments. At the mRNA level amounts of Galphai1 increased significantly (P < 0.01) in neostriatum. Galphas messenger amounts decreased in frontal cortex and increased in thalamus. These effects were common for both drugs, however, in addition also some differential effects, specific for either of the two drugs, were observed. We conclude frontal cortex and neostriatum are important target regions of long-term treatment with either lithium or carbamazepine and suggest Galphao, Galphas, Galphai1 and Gbeta to be selective target molecules.
Jakobsen
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Department of Biological Psychiatry, Psychiatric Hospital, Risskov, Denmark.
Wiborg
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O
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000737:chemistry*; D008032:Limbic System / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D010446:Peptide Fragments; D012333:RNA, Messenger; D002220:Carbamazepine; D008094:Lithium; D019204:GTP-Binding Proteins